This chapter focuses on the structure of proteins and how it relates to their functions. When a protein folds, it generally segregates the hydrophobic side chains in the interior of the protein, where they interact with one another away from water molecules in the cytoplasm. Protein structure is held together by hydrogen bonds and disulfide bridges between cysteine residues. Proteins can be denatured by treatments that break these bonds, such as heat or harsh chemicals. If a protein is denatured, it often cannot refold itself even if the denaturing agent is removed. Proteins carry out functions through molecular interactions between specific side chains and their targets. Scientists also learn about new proteins by comparing their amino acid sequences to the sequences of all other known proteins, using national databases and search engines. Researchers are using their knowledge of protein structure and protein function to improve the usefulness of enzymes in industrial and other processes. They do this by manipulating the DNA sequences of genes encoding these proteins, so that the proteins can have altered amino acid sequences and characteristics.

Peptide bonds. (A) Peptide bonds are formed between the NH2 group of one amino acid and the COOH group of another, with the formation and loss of a water molecule. Rn, amino acid side chain. (B) A protein has a polypeptide backbone with various amino acid side chains.

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Figure 5.2

Peptide bonds. (A) Peptide bonds are formed between the NH2 group of one amino acid and the COOH group of another, with the formation and loss of a water molecule. Rn, amino acid side chain. (B) A protein has a polypeptide backbone with various amino acid side chains.

A polar chemical bond. Although the oxygen and hydrogen nuclei share electrons, the highly electronegative oxygen nucleus tends to draw them away from the weakly electronegative hydrogen nucleus. As a result, the oxygen end of the bond acquires a partial negative charge, while the hydrogen end is partially positive.

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Figure 5.3

A polar chemical bond. Although the oxygen and hydrogen nuclei share electrons, the highly electronegative oxygen nucleus tends to draw them away from the weakly electronegative hydrogen nucleus. As a result, the oxygen end of the bond acquires a partial negative charge, while the hydrogen end is partially positive.

Domain structures of some modular proteins. Epidermal growth factor (EGF) is a protein that signals several cell types to divide. The other four proteins are protein-digesting enzymes with a variety of physiological roles.

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Figure 5.14

Domain structures of some modular proteins. Epidermal growth factor (EGF) is a protein that signals several cell types to divide. The other four proteins are protein-digesting enzymes with a variety of physiological roles.

Keratin, a structural protein. (A) The keratin polypeptide forms an alpha helix with hydrophobic side chains (not shown). (B) Two keratin helices wrap tightly around one another. (C) The coiled helices lie side by side and end to end, forming fibers.

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Figure 5.15

Keratin, a structural protein. (A) The keratin polypeptide forms an alpha helix with hydrophobic side chains (not shown). (B) Two keratin helices wrap tightly around one another. (C) The coiled helices lie side by side and end to end, forming fibers.

Protein stability engineering. Three engineered disulfide bridges (gold) tie the two domains of bacteriophage T4 lysozyme in the proper configuration. The two domains are shown in lavender and green. The numbers indicate the positions of the cysteines in the 164-amino-acid polypeptide. The cysteine at position 54 was changed to a threonine to keep it from interfering with proper formation of the engineered bridges. (Adapted from M. Matsumara, G. Signor, and B.W. Matthews, Nature 342:291, 1989, with permission.)

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Figure 5.19

Protein stability engineering. Three engineered disulfide bridges (gold) tie the two domains of bacteriophage T4 lysozyme in the proper configuration. The two domains are shown in lavender and green. The numbers indicate the positions of the cysteines in the 164-amino-acid polypeptide. The cysteine at position 54 was changed to a threonine to keep it from interfering with proper formation of the engineered bridges. (Adapted from M. Matsumara, G. Signor, and B.W. Matthews, Nature 342:291, 1989, with permission.)